Case 1
A 18 year old male presented with history of fever and headache for 3 days duration. Complete blood count showed haemoglobin of 6.6 g/dL, white blood cells 1.3 x 109/L, platelet count 10 x 109/L and 49% blasts in differential count. Bone marrow examination showed 89% blasts. Flow cytometry analysis was suggestive of ETP – ALL [CD7(bright), CD33+, CD 38+, hetergenous dim to moderate CD5, 64% blasts positive for CD34, cCD3 positive. Negative expression was seen for CD1a, CD2, CD3, CD4, CD8, CD10, CD13, CD15, CD16, CD19, CD34, c CD41, CD56, cCD 79a, cMPO and cTdT). Molecular markers were negative. He had complex karyotype (46, XY, add(10)(q26), del(11)(q13q23),del(12)(q13),-15,-17, add(20)(q13.3), del(20)(q13.1), +mar1, +mar2[10]). Baseline cerebrospinal fluid examination was normal. He was started on Berlin-Frankfurt-Meunster (BFM) 95 ALL protocol. Day 8 blast count was 0.35 x109/L. He developed febrile neutropenia with probable fungal pneumonia. Post induction bone marrow examination showed persistence of 10% blasts. He was started on HR 1 protocol of BFM 95 along with oral venetoclax x 7 days (100 mg day 1, 200 mg day2, 300 mg day3, and 100 mg with oral posaconazole from day 4 to day 7). Post HR1, he developed febrile neutropenia with fungal pneumonia. Repeat bone marrow examination on day 28 showed morphological remission with negative minimal residual disease MRD (<0.01%). He received HR 2 protocol with venetoclax (100 mg for 7 days along with oral posaconazole). Following recovery, he underwent matched sibling donor allogeneic stem cell transplant. Conditioning was given with cyclophosphamide 60 mg /kg x 2 days on D-5, D-4 followed by myeloablative total body irradiation – 200 Gy twice a day x 3 days on D-3, D-2 and D-1. Graft versus host disease prophylaxis was given with tacrolimus and short course methotrexate on D1, 3, 6 and 11. He achieved neutrophil engraftment on day + 15 and platelet engraftment on day + 9. Day+ 30 chimerism was 100 % donor. Day +60 bone marrow evaluation showed morphological remission and negative MRD (<0.01%). He developed tacrolimus toxicity in the form of severe tremors and seizures. MRI brain and CSF analysis were normal. Tacrolimus tapering was started on day + 88 and tacrolimus was stopped on day + 100. At present he has completed 2 years 1 month of follow-up and is on weekly 15 mg methtrxate for chronic skin graft versus host disease (GVHD).